This is now in an active data gathering phase. As osteosarcoma is a rare cancer, obtaining suitable biospecimens is a major obstacle to studying this disease. To overcome this problem it has been necessary to reach outside of the intramural community. A collaboration to obtain specimens has been established with the Childrens Oncology Group (COG), the primary national cooperative clinical trials group for pediatric cancer, to sequence specimens collected under COG trial. As osteosarcoma had been selected by the TARGET project (NCIs Therapeutically Applicable Research to Generate Effective Treatments, http://target.cancer.gov/about/), the TARGET infrastructure has been used to facilitate the COG collaboration. This collaboration will provide samples for analysis. An additional aspect of the early phase of this project has been the development of the necessary sequencing infrastructure. Suitable sequencing and computational equipment has been installed to support this project, and the bioinformatics infrastructure for data analysis has also been developed. Data generation has been completed on a panel of osteosarcoma cell lines. This will be highly useful for the long term goals of the project since well characterized cell lines can be used for functional investigation of the biologically important results obtained in the course of this research. We have now initiated the analysis of clinical biospecimens collected through the TARGET program. This entails the sequencing of exomes, transcriptomes, and, from selected specimens, whole genomes. A large proportion of the data has been collected, and is now entering the analysis phase. Analysis will use standard and novel methods. This will be followed by technical validation, prevalence determination, and biological investigation of principle leads arising from this discovery phase.